Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: PMPCB

Gene summary for PMPCB

Gene summary.

Gene information	Species	Human
	Gene symbol	PMPCB
	Gene ID	9512
	Gene name	peptidase, mitochondrial processing subunit beta
	Gene Alias	Beta-MPP
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	B3KM34

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
9512	PMPCB	LZE2T	Human	Esophagus	ESCC	8.94e-10	6.52e-01	0.082
9512	PMPCB	LZE4T	Human	Esophagus	ESCC	1.14e-12	3.81e-01	0.0811
9512	PMPCB	LZE5T	Human	Esophagus	ESCC	5.38e-05	1.48e-01	0.0514
9512	PMPCB	LZE7T	Human	Esophagus	ESCC	6.40e-09	5.69e-01	0.0667
9512	PMPCB	LZE8T	Human	Esophagus	ESCC	3.65e-07	2.02e-01	0.067
9512	PMPCB	LZE20T	Human	Esophagus	ESCC	7.50e-06	1.95e-01	0.0662
9512	PMPCB	LZE22T	Human	Esophagus	ESCC	1.04e-03	3.21e-01	0.068
9512	PMPCB	LZE24T	Human	Esophagus	ESCC	1.42e-20	6.05e-01	0.0596
9512	PMPCB	P1T-E	Human	Esophagus	ESCC	3.65e-06	5.09e-01	0.0875
9512	PMPCB	P2T-E	Human	Esophagus	ESCC	1.89e-80	1.47e+00	0.1177
9512	PMPCB	P4T-E	Human	Esophagus	ESCC	9.49e-41	1.02e+00	0.1323
9512	PMPCB	P5T-E	Human	Esophagus	ESCC	5.99e-22	5.01e-01	0.1327
9512	PMPCB	P8T-E	Human	Esophagus	ESCC	3.17e-22	3.29e-01	0.0889
9512	PMPCB	P9T-E	Human	Esophagus	ESCC	2.01e-16	4.61e-01	0.1131
9512	PMPCB	P10T-E	Human	Esophagus	ESCC	2.49e-32	5.49e-01	0.116
9512	PMPCB	P11T-E	Human	Esophagus	ESCC	2.16e-15	5.86e-01	0.1426
9512	PMPCB	P12T-E	Human	Esophagus	ESCC	1.01e-51	1.09e+00	0.1122
9512	PMPCB	P15T-E	Human	Esophagus	ESCC	3.38e-52	1.24e+00	0.1149
9512	PMPCB	P16T-E	Human	Esophagus	ESCC	9.40e-61	1.12e+00	0.1153
9512	PMPCB	P17T-E	Human	Esophagus	ESCC	1.09e-19	1.01e+00	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006605111	Esophagus	ESCC	protein targeting	229/8552	314/18723	4.93e-23	1.01e-20	229
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:0072655110	Esophagus	ESCC	establishment of protein localization to mitochondrion	97/8552	120/18723	2.17e-15	1.33e-13	97
GO:0070585110	Esophagus	ESCC	protein localization to mitochondrion	100/8552	125/18723	2.96e-15	1.77e-13	100
GO:0006626110	Esophagus	ESCC	protein targeting to mitochondrion	81/8552	100/18723	3.60e-13	1.67e-11	81
GO:005160418	Esophagus	ESCC	protein maturation	189/8552	294/18723	7.64e-11	2.39e-09	189
GO:001648514	Esophagus	ESCC	protein processing	134/8552	225/18723	1.81e-05	1.60e-04	134
GO:007259412	Liver	Cirrhotic	establishment of protein localization to organelle	189/4634	422/18723	1.01e-19	2.45e-17	189
GO:00066057	Liver	Cirrhotic	protein targeting	148/4634	314/18723	3.86e-18	6.20e-16	148
GO:00068397	Liver	Cirrhotic	mitochondrial transport	112/4634	254/18723	1.03e-11	6.66e-10	112
GO:00705857	Liver	Cirrhotic	protein localization to mitochondrion	65/4634	125/18723	4.91e-11	2.77e-09	65
GO:00726557	Liver	Cirrhotic	establishment of protein localization to mitochondrion	63/4634	120/18723	5.70e-11	3.19e-09	63
GO:00516046	Liver	Cirrhotic	protein maturation	121/4634	294/18723	3.54e-10	1.68e-08	121
GO:00066267	Liver	Cirrhotic	protein targeting to mitochondrion	53/4634	100/18723	1.19e-09	5.27e-08	53
GO:00164853	Liver	Cirrhotic	protein processing	85/4634	225/18723	9.01e-06	1.32e-04	85
GO:007259422	Liver	HCC	establishment of protein localization to organelle	299/7958	422/18723	1.06e-32	6.10e-30	299
GO:000660512	Liver	HCC	protein targeting	219/7958	314/18723	7.74e-23	1.49e-20	219
GO:000683912	Liver	HCC	mitochondrial transport	184/7958	254/18723	2.30e-22	3.83e-20	184
GO:007265512	Liver	HCC	establishment of protein localization to mitochondrion	98/7958	120/18723	1.18e-18	1.46e-16	98

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

PMPCB

SNV

Missense_Mutation

c.1300C>G

p.Pro434Ala

p.P434A

O75439

protein_coding

deleterious(0.02)

possibly_damaging(0.899)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

PMPCB

SNV

Missense_Mutation

c.1204N>C

p.Asn402His

p.N402H

O75439

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-E2-A1B5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PMPCB

insertion

Nonsense_Mutation

novel

c.980_981insGTAATGTACATCACATTATACCACCTAGGGTTTA

p.Phe327LeufsTer2

p.F327Lfs*2

O75439

protein_coding

TCGA-A2-A04V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PMPCB

insertion

In_Frame_Ins

novel

c.150_151insCATCCTTCATCCTCTACCTTCCTTCTAGCAGAAATGGCG

p.Gln50_Val51insHisProSerSerSerThrPheLeuLeuAlaGluMetAla

p.Q50_V51insHPSSSTFLLAEMA

O75439

protein_coding

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

PMPCB

insertion

In_Frame_Ins

novel

c.327_327+1insTTTAATATCAGATTAGTAATGTGTTTT

p.Lys109_Gly110insPheAsnIleArgLeuValMetCysPhe

p.K109_G110insFNIRLVMCF

O75439

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

PMPCB

SNV

Missense_Mutation

novel

c.1196N>A

p.Arg399Gln

p.R399Q

O75439

protein_coding

deleterious(0.02)

probably_damaging(0.968)

TCGA-VS-A9V3-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PMPCB

SNV

Missense_Mutation

c.339G>C

p.Lys113Asn

p.K113N

O75439

protein_coding

tolerated(0.25)

benign(0.047)

TCGA-AG-A026-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Unknown

PMPCB

SNV

Missense_Mutation

novel

c.1342N>C

p.Glu448Gln

p.E448Q

O75439

protein_coding

tolerated(0.64)

benign(0)

TCGA-AH-6544-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

PMPCB

SNV

Missense_Mutation

rs139269263

c.212C>T

p.Ser71Leu

p.S71L

O75439

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

PMPCB

SNV

Missense_Mutation

rs200188353

c.524N>A

p.Arg175His

p.R175H

O75439

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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